Androgen induced growth factor (AIGF) is a factor isolated in 1992 from a culture supernatant of a mouse mammary tumor cell line SC-3 [Shionogi Carcinoma-3: J. Steroid Biochem., 27, 459 (1987)] which shows sex hormone-dependent growth. AIGF is a growth factor which is induced and produced by androgen stimulation and activates growth of SC-3 cells in an autocrine manner [Proc. Natl. Acad. Sci., 89, 8928–8932, (1992)]. The results of gene cloning efforts revealed that it has a homology of 30 to 40% with the FGF family at the amino acid level, and it was named fibroblast growth factor-8 (hereinafter referred to as “FGF-8”). Thereafter, human FGF-8 was cloned from a human placenta genomic library using mouse FGF-8 as a probe, which coincided with the mouse FGF-8 by a factor of 85% at the nucleotide level and 100% at the amino acid level [FEBS Letters, 363, 226 (1995)]. It has been assumed that sex hormone induced growth factors would exhibit an autocrine role in tumors such as prostatic cancer, and breast cancer which show sex hormone-dependent growth, and the isolation and cloning of FGF-8, though in a mouse system, was the first evidence of such a mechanism. It is probable that FGF-8 also plays a role in carcinogenesis and tumor growth in humans by a similar mechanism, but clear evidence has not yet been obtained. However, since expression of FGF-8 m-RNA can be found in several human tumor cell lines of prostatic cancer and breast cancer and enhancement of cell growth can be observed when FGF-8 expressed in CHO cells is added to the culture system of these cell lines or a cell line of fibroblasts [FEBS Letters, 363, 226 (1995)], expression of mRNA in various human cancer cell lines such as prostate cancer, breast cancer and ovarian cancer was confirmed [Cell Growth & Differ., 7, 1425 (1996), Oncogene, 18, 1053 (1999), Int. J. Cancer, 88, 718 (2000)] and FGF-8s presented in human cancer tissues of prostate cancer, breast cancer and ovarian cancer was over-expressed compared to FGF-8s presented in normal tissues [Cancer Res., 58, 2053, Oncogene, 18, 2755 (1999), Oncogene, 18, 1053 (1999), Int. J. Cancer, 88, 718 (2000)], such a possibility has been pointed out that FGF-8 also plays an autocrine and paracrine role on the sex hormone-dependent growth of cancer cells in human. On the other hand, since high frequency expression of FGF-8 has also been observed in various hormone-independent human prostate cancer cells, prostate cancer tissues and breast cancer cells [Cell Growth & Differ., 7, 1425 (1996), Oncogene, 18, 2755 (1999), Oncogene, 18, 1053 (1999)], there is a high possibility that expression of FGF-8 is controlled by sex hormone independent fashion. Furthermore, since there is a report that antisense DNA for FGF-8 inhibited in vitro and in vivo growth of a hormone-independent prostate cancer cell line [Oncogene, 16, 1487 (1998)], the presence of an FGF-8-dependent growth mechanism is also suggested in cancers which lost hormone-dependency.
Based on these facts, antibodies against FGF-8 are effective in analyzing biological function of FGF-8 for cancer cells and also in diagnosing cancer cells such as prostate cancer and breast cancer using an immunological detection method. Furthermore, in neutralizing antibodies which inhibits functions of FGF-8, it is expected that they are useful for analyzing the biological function of FGF-8, diagnosing cancers such as prostate cancer, breast cancer and ovarian cancer and treating sex hormone-dependent cancers and sex hormone-independent cancers.
In consequence, an antibody specific for FGF-8 is useful for the analysis of the role and biological function of FGF-8 in the above-mentioned tumor cells, and also for the diagnosis of prostatic cancer, breast cancer and the like by immunological detection. Also, it appears that the antibody having a neutralization activity would be useful in studying biological activities of FGF-8 and effective in treating the cancers.
To date the isolation of a monoclonal antibody specific for FGF-8 has nor been reported.